PASS Scripta Varia 21 - Pontifical Academy of Sciences

THERAPEUTIC VACCINES AGAINST CANCER AND AUTOIMMUNE DISEASES
oped Cop 1-reactive antibodies, which peaked at 3 months after initiation
of treatment, decreased at 6 months, and then remained low. The proliferative
response of peripheral blood mononuclear cells to Cop 1 was high
initially and gradually decreased during treatment. Several studies showed
that MS patients mainly produce the Th2 type of GA-specific T cells after
receiving GA (13,14). Cross-reactivity between GA and MBP is seen at
several levels: antibodies, T cells, and cross-triggering of cytokines.
Disseminated demyelination is the primary morphological hallmark
characterizing multiple sclerosis (MS) and its animal model, experimental
autoimmune encephalomyelitis (EAE), leading to axonal loss and neurological
impairments. It is, therefore, important to evaluate MS treatments
for their neuroprotective capability to prevent demyelination and/or enhance
remyelination. The interplay between pathological demyelination and
the corresponding repair mechanism remyelination involves, on the one
hand, the inflammatory immune cells that mediate the damage and on the
other hand, the myelin-producing cells, the oligodendrocytes. The latter are
terminally differentiated cells with a limited capacity to respond to injury
that are destroyed in the actively demyelinating lesions. Accordingly, remyelination
requires the recruitment of oligodendrocyte precursor cells
(OPCs) by their proliferation and migration into the demyelinating area
and their further differentiation into mature myelinating oligodendrocytes
through distinct stages characterized by morphological transformation, and
sequential expression of developmental markers.
The interplay between demyelination and remyelination is critical in
the progress of MS and its animal model EAE. In a recent study (15), we
explored the capacity of glatiramer acetate (GA, Copaxone) to affect the
demyelination process and/or lead to remyelination in mice inflicted by
chronic EAE, using both scanning electron microscopy and immunohistological
methods. Spinal cords of untreated EAE mice revealed substantial
demyelination accompanied by tissue destruction and axonal loss. In contrast,
in spinal cords of GA-treated mice, in which treatment started concomitantly
with disease induction (prevention), no pathology was observed.
Moreover, when treatment was initiated after the appearance of clinical
symptoms (suppression) or even in the chronic disease phase (delayed suppression)
when substantial demyelination was already manifested, it resulted
in a significant decrease in the pathological damage.
Presently, Copaxone (GA, Cop 1) is the most used drug against multiple
sclerosis. It has already crossed one million years of use without significant
side effects.
The Scientific Legacy of the 20 th Century
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